Project Summary The long-range goal of this research is to understand the cellular and molecular mechanisms that mediate the normal performance and adaptive plasticity of smooth eye movements. The optokinetic reflex (OKR) prevents blurred vision during self-motion by producing smooth eye movements that compensate for full field image motion. Neuronal mechanisms of plasticity enable the OKR to adapt in the face of development, trauma, and disease. Although the roles of particular classes of neurons to signal transformations and plasticity have been identified, little is understood about how cellular mechanisms contribute to the day-to-day performance and adaptive capabilities of the OKR and other smooth eye movements. The objective of the proposed research is to elucidate how cerebellar activity influences signaling and plasticity in distinct classes of brainstem neurons responsible for smooth eye movements. The central hypothesis is that cerebellar and visual pathway synapses onto vestibular nucleus and nucleus prepositus hypoglossi neurons are differentially responsible for rapid initiation vs maintained components of smooth eye movements. The proposed research will examine the influence of cerebellar activity on eye movements evoked by moving visual stimuli. Cellular and synaptic physiological experiments in brainstem slice preparations will examine the short and long term dynamics of cerebellar and visual synapses onto cerebellar recipient neurons, which mediate cerebellar influences on signaling and plasticity on smooth eye movements. Distinct classes of cerebellar target neurons will be identified by their axonal projections and patterns of cerebellar synaptic cell terminals. The influence of visual pathway and cerebellar synaptic activity will be examined in cerebellar target neurons in the vestibular and prepositus nuclei. These studies will provide foundations for targeted investigations of the molecular mechanisms that mediate smooth eye movements as well as for pharmacological treatments of cerebellar disorders and of oculomotor disorders that cause nystagmus.